Neoadjuvant Treatment Adherence Predicts Advanced Rectal Cancer Outcomes

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Neoadjuvant chemoradiotherapy (nCRT) adherence is linked to 3-year disease-free survival (DFS) outcomes for patients with T3–T4 node-positive rectal cancer, say the CAO/ARO/AIO-04 trial investigators. 

Post-hoc analysis of the phase III trial showed that 67.0% of the 625 patients randomly assigned to receive fluorouracil-based nCRT completed their full course of 50.4 Gy with concurrent chemotherapy, as did 71.5% of the 607 patients given the nCRT plus oxaliplatin.

Of the patients who went on to receive curative surgery and adjuvant chemotherapy, the full adjuvant regimen was completed by 57.6% of the 439 patients given only fluorouracil-based treatment versus 32.0% of the 419 patients who also received oxaliplatin, say Markus Diefenhardt, from the University of Frankfurt in Germany, and co-workers.

After a median 50 months of follow-up, 3-year DFS was achieved by 71.1% of the nCRT arm and 75.8% of the nCRT plus oxaliplatin arm, giving a significant hazard ratio (HR) of 0.803 in favour of oxaliplatin use. 

Patients who completed the full course of nCRT alone or alongside oxaliplatin had slightly better 3-year DFS than those who nearly completed treatment, defined as receipt of 45 Gy or more plus at least 80% of chemotherapy, with HRs of 1.325 and 1.501, respectively.  

But the difference in 3-year DFS rates reached significance when patients who completed nCRT alone or with oxaliplatin were compared with those who had received less than 45 Gy or less than 80% of chemotherapy, with HRs of 1.877 and 1.724, respectively. 

The investigators hypothesise that previously reported negative results in “studies with oxaliplatin may be explained, at least in part, by impaired adherence to nCRT in the experimental groups.”

However, adherence to adjuvant chemotherapy did not have a significant impact on 3-year DFS in either the fluorouracil alone or with oxaliplatin treatment arms, say the researchers who describe the role of adjuvant chemotherapy for rectal cancer as “opaque” following the lack of benefit in five phase II/III randomised trials. 

The team reports that DFS was significantly associated with ECOG performance status in both treatment arms, tumour localisation in the fluorouracil-only arm and age in the oxaliplatin arm.  

Noting that 60–67% of patients in the current trial arms were aged at least 70 years and 62–66% had an ECOG score of 1–2, the team believes that “age and performance status did not prohibit administration of oxaliplatin.” 

The investigators write in JAMA Oncology: “These data reflect the importance of optimal dosing and supportive strategies to facilitate adherence to nCRT, especially among older patients and those with poor performance status.”  

Acknowledging that fluorouracil-based nCRT plus oxaliplatin had previously been found to be well tolerated in a phase I/II study, the authors conclude that such early studies are “essential to establish optimal nCRT dosing, while close monitoring and supportive measures to increase adherence to nCRT should be implemented as an integral part of study design.” 

They add: “A shift toward total neoadjuvant treatment, rather than [adjuvant chemotherapy], may increase adherence to systemic treatment and potentially increase DFS.” 

Reference 

Diefenhardt M, Ludmir EB, Hofheinz R-D, et al. Association of treatment adherence with oncologic outcomes for patients with rectal cancer. A post hoc analysis of the CAO/ARO/AIO-04 phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 9 July 2020. doi:10.1001/jamaoncol.2020.2394